CHROMIC: 11 Adverse Event Reports & Safety Profile

DESCRIPTION Chromium 4 mcg/mL (Chromic Chloride Injection, USP) is a sterile, nonpyrogenic solution intended for use as an additive to intravenous solutions for total parenteral nutrition (TPN). Each mL of solution contains 20.5 mcg chromic chloride, hexahydrate and 9 mg sodium chloride. The solution contains no bacteriostat, antimicrobial agent, or added buffer. The pH is 2.0 (1.5 to 2.5); product may contain hydrochloric acid and/or sodium hydroxide for pH adjustment. The osmolarity is 0.308 mOsm/mL (calc.).

Chromic

Chloride, USP is chemically designated chromic chloride, hexahydrate CrCl 3

• 6H 2 O, a crystalline compound soluble in water.

Sodium

Chloride, USP is chemically designated NaCl, a white, crystalline compound freely soluble in water. The semi-rigid vial is fabricated from a specially formulated polyolefin. It is a copolymer of ethylene and propylene. The safety of the plastic has been confirmed by tests in animals according to USP biological standards for plastic containers. The small amount of water vapor that can pass through the plastic container wall will not significantly alter the drug concentration.

INDICATIONS AND USAGE This formulation is indicated for use as a supplement to intravenous solutions given for TPN for children up to 11 years of age. Administration of the solution in TPN solutions helps to maintain plasma levels of zinc, copper, manganese, and chromium and to prevent depletion of endogenous stores of these trace elements and subsequent deficiency symptoms.

DOSAGE AND ADMINISTRATION Each mL of the solution provides Zinc 1 mg, Copper 0.4 mg, Manganese 0.1 mg, Chromium 4 mcg, and Selenium 20 mcg. The suggested dosage ranges for the five trace elements are: ZINC : For the metabolically stable adult receiving TPN, the suggested intravenous dosage level is 2.5 to 4 mg zinc/day. An additional 2 mg zinc/day is suggested for acute catabolic states. For the stable adult with fluid loss from the small bowel, an additional 12.2 mg zinc/liter of small bowel fluid lost, or an additional 17.1 mg zinc/kg of stool or ileostomy output is recommended. Frequent monitoring of zinc blood levels is suggested for patients receiving more than the usual maintenance dosage level of zinc. Normal plasma levels for zinc vary from approximately 88 to 112 mcg/100 mL. For full term infants and children up to 5 years of age, 100 mcg zinc/kg/day is recommended. For premature infants (birth weight less than 1500 g) up to 3 kg in body weight, 300 mcg zinc/kg/day is suggested. COPPER : For the metabolically stable adult receiving TPN, the suggested additive dosage level is 0.5 to 1.5 mg copper/day. For pediatric patients, the suggested additive dosage level is 20 mcg copper/kg/day. The normal plasma range for copper is approximately 80 to 160 mcg/100 mL. MANGANESE : For the metabolically stable adult receiving TPN, the suggested additive dosage level for manganese is 0.15 mg to 0.8 mg/day. For pediatric patients, a dosage level of 2 to 10 mcg manganese/kg/day is recommended. CHROMIUM : For the metabolically stable adult receiving TPN, the suggested additive dosage level is 10 to 15 mcg chromium/day. The metabolically stable adult with intestinal fluid loss may require 20 mcg chromium/day, with frequent monitoring of blood levels as a guideline for subsequent administration. For pediatric patients, the suggested additive dosage level is 0.14 to 0.20 mcg/kg/day. SELENIUM : For metabolically stable adults receiving TPN, the suggested additive dosage level is 20 to 40 mcg selenium/day. For pediatric patients, the suggested additive dosage level is 3 mcg/kg/day. In adults, selenium deficiency states resulting from long term TPN support, selenium as selenomethionine or selenious acid, administered intravenously at 100 mcg/day for a period of 24 and 31 days, respectively, has been reported to reverse deficiency symptoms without toxicity. The normal whole blood range for selenium is approximately 10 to 37 mcg/100 mL. Periodic monitoring of plasma levels of Zinc, Copper, Manganese, Chromium and Selenium is suggested as a guideline for administration. Aseptic addition of MULTITRACE ® - 5 to parenteral nutrition solutions under laminar flow hood is recommended. The trace elements present in MULTITRACE ® - 5 are physically compatible with the electrolytes and vitamins usually present in parenteral nutrition formulations. Do not directly mix ascorbic acid injection with copper or selenium containing parenteral products in the same syringe or vial, as this admixture may cause the formation of an insoluble precipitate. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) (See USP Controlled Room Temperature).

CONTRAINDICATIONS MULTITRACE ® - 4 PEDIATRIC should not be given undiluted by direct injection into a peripheral vein because of the potential of infusion phlebitis.

ADVERSE REACTIONS The amounts of ZINC, COPPER, MANGANESE, CHROMIUM and SELENIUM in the solution are very small and toxicity symptoms due to these trace elements at suggested dosage levels are considered unlikely to occur.

WARNINGS Direct intramuscular or intravenous injection of Chromium 4 mcg/mL (Chromic Chloride Injection, USP) is contraindicated, as the acidic pH of the solution may cause considerable tissue irritation. Severe kidney disease may make it necessary to reduce or omit chromium and zinc doses because these elements are primarily eliminated in the urine. WARNING: This product contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum. Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.

PRECAUTIONS General Do not use unless solution is clear and seal is intact.

Chromium

4 mcg/mL (Chromic Chloride Injection, USP) should only be used in conjunction with a pharmacy directed admixture program using aseptic technique in a laminar flow environment; it should be used promptly and in a single operation without any repeated penetrations. Solution contains no preservatives; discard unused portion immediately after admixture procedure is completed. In assessing the contribution of chromium supplements to maintenance of glucose homeostasis, consideration should be given to the possibility that the patient may be diabetic.

Geriatric

Use An evaluation of current literature revealed no clinical experience identifying differences in response between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Laboratory Tests

Because chromium is present in the bloodstream in microgram quantities, routine measurement is impractical. If necessary, samples can be sent to a reference laboratory for assay. Carcinogenesis, Mutagenesis, and Impairment of Fertility Long-term animal studies to evaluate the carcinogenic potential of Chromium 4 mcg/mL (Chromic Chloride Injection, USP) have not been performed, nor have studies been done to assess mutagenesis or impairment of fertility.

Nursing

Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Chromium 4 mcg/mL (Chromic Chloride Injection, USP) is administered to a nursing woman.

Pediatric Use

See DOSAGE and ADMINISTRATION section. Safety and effectiveness in children have not been established.

Pregnancy

Animal reproduction studies have not been conducted with chromic chloride. It is also not known whether chromic chloride can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Chromic chloride should be given to a pregnant woman only if clearly indicated.